The University of Pittsburgh Brain Injury System (UPBI) has been established as a clinical care and research center to serve the entire population of western Pennsylvania and portions of northern West Virginia and eastern Ohio. The need for a TBI clinical trials network is evidenced by the conclusions of the 1998 NIH TBI conference. The investigators feel that understanding the mechanisms that impact recovery and interventional efficacy, as well as the establishment of proxy measures that can predict long term outcome is an important role of the TBI clinical trials network. The UPBI spans from injury site to community and from the University's fundamental research labs to the homes of local adults and children with TBI. The UPBI provides state of the art care for and acquires data on over 300 severe and moderately injured adults and children each year. The follow-up rate of over 90% is a testament to the extensive resources that have been committed to this program. The UPBI is cornerstoned by a key group of investigators and consultants with a history of successful collaborative TBI clinical research. Specifically, the TBI research focus includes (1) mechanisms of injury and recovery of dopamine systems, (2) gender related differences in injury, recovery, and response to therapies, and (3) genetic influences on mechanisms of injury, recovery, and pharmacotherapeutic efficacy. Special emphasis has been placed on the study of the effects of methylphenidate on executive functioning and outcome after TBI and the influence of gender and dopamine transporter genotype on therapeutic efficacy of this drug. UPBI participation in the TBI clinical trials network will serve to enhance the UPBI in achieving its aims and goal of providing excellent clinical care, continuing participation in TBI clinical trials, developing methods and measures of objective and meaningful outcome, and evaluating specific pharmacological and therapeutic interventions for improved outcomes with TBI. Through its participation, the UPBI hopes to help fulfill the NIH recognized objective to evaluate, through multiple centers using common protocols, the relationship between acute care practice andrehabilitation strategies to the long-term functional outcome of TBI patients.